This journal is c The Royal Society of Chemistry 2011 Chem. Commun., 2011, 47, 12089–12091 12089

Cite this: Chem. Commun., 2011, 47, 12089–12091

Application of a chiral metal–organic framework in enantioselective

separationw

Mohan Padmanaban,aPhilipp Muller,

bChristian Lieder,

cKristina Gedrich,

bRonny Grunker,

b

Volodymyr Bon,bIrena Senkovska,

bSandra Baumgartner,

cSabine Opelt,

cSilvia Paasch,

d

Eike Brunner,dFrank Glorius,*

aElias Klemm*

cand Stefan Kaskel*

b

Received 8th August 2011, Accepted 16th September 2011

DOI: 10.1039/c1cc14893a

A modular approach for the synthesis of highly ordered porous and

chiral auxiliary (Evans auxiliary) decorated metal–organic frame-

works is developed. Our synthesis strategy, which uses known

porous structures as model materials for incorporation of chirality

via linker modification, can provide access to a wide range of

porous materials suitable for enantioselective separation and cata-

lysis. Chiral analogues of UMCM-1 have been synthesized and

investigated for the enantioseparation of chiral compounds in the

liquid phase and first promising results are reported.

Metal–organic frameworks (MOFs) are highly porous, crystalline

coordination polymers generated from metal atoms or clusters

as ‘‘nodes’’ and organic linkers as nodal ‘‘connectors’’.1

Following their recent development, MOFs have found several

attractive applications, including gas separation, gas storage

and selective catalysis.2 Among others, the properties and

utilities of the MOFs depend on their pore size and shape,

the interior and exterior surfaces, and the functional groups

employed. Intriguingly, the properties of the MOFs can be

easily modified, but minor changes in the synthetic process,

linker or the metal often lead to the dramatic changes in their

structure and properties.3

Whereas various porous materials including zeolites,

activated carbon, silica gel and various polymer resins have been

shown to be useful stationary phases in gas chromatography,4

liquid chromatography5 and electrochromatography, MOFs

are far less explored. Recently, it has been shown that MOFs

are able to separate mixtures of compounds in small volumes.6

Because of their defined architectures, accessible volumes,

pore size etc., these porous solids can be used as a promising

stationary phase for the separation of organic compounds.

Moreover, examples of in situ incorporation of chiral auxili-

aries into MOF building blocks followed by their subsequent

utilization in the enantioseparation are rare and to the best of

our knowledge no high performance liquid chromatography

(HPLC) enantioseparation by chiral porous MOFs has been

reported so far.

One possible way to form chiral materials is utilizing privileged

chiral ligands like BINOL or BINAP in the construction of

MOFs.7 Thereby, amorphous solids are generally obtained and

control of the resulting topology and porosity is difficult.7,8 An

alternative strategy is the attachment of chiral auxiliaries to well-

known linkers, either by postsynthetic modification9 or by starting

from auxiliary substituted linkers in the first place. In the latter

case, the synthesis of MOFs with desired chemical inter-

actions, topology, and pore sizes seems to be within reach.3a

Herein we report the synthesis, structural characterization,

and separation performance of chiral modified UMCM-1

structure (Chir-UMCM-1). UMCM-1 (Zn4O(BTB)4/3(BDC))

was discovered by Matzger et al. and is a high surface area

mesoporous MOF which consists of 1,4-benzenedicarboxylate

(BDC) and benzene-1,3,5-tribenzoate (BTB) linkers.10 In the

Chir-UMCM-1 reported here, the BDC linker was replaced

with chiral auxiliary substituted BDC (ChirBDC).

For the ChirBDC linker synthesis, 2-bromoterephthalic acid

was converted into dimethyl 2-bromoterephthalate. This was

coupled with enantiopure chiral (S)-oxazolidinone (Evans

auxiliary)11 in the presence of CuI, K2CO3 and dimethylethylene

diamine in toluene. Chiral auxiliary substituted BDCs

were obtained by basic hydrolysis of the corresponding esters

(Scheme S1, ESIw). The linkers were used for the synthesis of

ChirMOFs.

We modified the ratio of reagents and reaction conditions of

the original UMCM-1 synthesis procedure in order to prevent

aWestfalische Wilhelms-Universitat, NRW Graduate School ofChemistry, Organisch-Chemisches Institut, Corrensstr. 40,48149 Munster, Germany. E-mail: glorius@uni-muenster.de;Fax: +49 251 8333202; Tel: +49 251 8333248

bDepartment of Inorganic Chemistry, Dresden University ofTechnology, Bergstr. 66, 01062 Dresden, Germany.E-mail: Stefan.Kaskel@chemie.tu-dresden.de;Fax: +49 351 46337287; Tel: +49 711 685 65590

c Institute of Chemical Technology, University of Stuttgart,Pfaffenwaldring 55, 70569 Stuttgart, Germany.E-mail: elias.klemm@itc.uni-stuttgart.de; Fax: +49 711 68564065;Tel: +49 351 46334885

dDepartment of Bioanalytical Chemistry, Dresden University ofTechnology, Bergstr. 66, 01062 Dresden, Germany.E-mail: eike.brunner@tu-dresden.de; Fax: +49 351 463 37188;Tel: +49 351 46332631

w Electronic supplementary information (ESI) available: Details of thesynthesis of Chir-BDC derivatives and MOFs, packing procedure anddetails of HPLCmeasurements, details of crystallographic measurements;1H and 13C NMR spectra, XRD patterns, N2 and H2 physisorptionisotherms. CCDC 831931 and 831930. For ESI and crystallographic datain CIF or other electronic format see DOI: 10.1039/c1cc14893a

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12090 Chem. Commun., 2011, 47, 12089–12091 This journal is c The Royal Society of Chemistry 2011

the formation of chiral MOF-5 analogue or MOF-177

(for more details see ESIw).Thus, Zn4O(BTB)4/3(iPr-ChirBDC)(DEF)19(H2O)6 (iPr-Chir-

UMCM-1, 1) and Zn4O(BTB)4/3(Bn-ChirBDC)(DEF)20(H2O)8(Bn-ChirUMCM-1, 2) were obtained as single phase materials

(the composition was derived from TGA and elemental analysis).

The powder (Fig. S1, ESIw) and single crystal X-ray diffraction

experiments revealed that the compounds are isotypic to

UMCM-1. The structures of 1 and 2 were refined in chiral

space group P63 with similar cell parameters.z This led to the

absence of an inversion center, which is present in UMCM-1

at the center of gravity of the BDC linker. The structures of

both compounds consist of Zn4O6+ clusters interconnected

into the 3D-network by 4 BTB and 2 substituted BDC linkers.

As expected, the framework structure, topology and pore

shape of Chir-UMCMs are similar to UMCM-1.10 Compound

1 exhibits positional disorder of the BDC oxazolidinone

substituent over two equally occupied positions, arranged on

the same side of the phenyl ring. Refinement of structure 2

shows disorder of the nitrogen atom of the oxazolidinone over

four positions. Unfortunately, only the nitrogen atom and not

the chiral substituent itself could be located crystallographically.

Hence, they were modelled separately for each position using

Forcite geometry optimization tool of Material Studio 5.0

(Accelrys Software, Inc., San Diego, CA, USA). It has been

shown that in both cases chiral substituents occupy the positions

in the trigonal microporous cages (Fig. 1). The successful

incorporation of the substituted BDC linker was proven via

IR, liquid and solid state NMR experiments (see ESIw).The 13C{1H} cross-polarization (CP) MAS NMR spectra of

compounds 1 (iPr-ChirUMCM-1) and 2 (Bn-ChirUMCM-1)

were measured at �26 1C (Fig. S19, ESIw). At this temperature,

the signals due to the chiral side groups are clearly detectable

in contrast to the room temperature spectra (Fig. S19, ESIw).It should be noted that the spectra in general exhibit a

pronounced temperature dependence which may be caused

by the presence of thermal motions within the relatively flexible

framework and/or minor temperature-induced structural

changes. Thermal motions lead to decreasing signal intensities

in CP spectra. The aforementioned signals due to the chiral

side groups are weak at room temperature but become more

intense at �26 1C. This behavior indicates the presence of

thermal motions especially for the side groups.

Solvent accessible voids, calculated using PLATON,12 are

79.4 and 78.2% for compounds 1 and 2, respectively, which

are slightly lower than for non-substituted UMCM-1 (82.8%).

The porous chiral framework could be also obtained after

solvent removal. The porosity of the activated compounds was

verified via nitrogen and hydrogen (Fig. S3, ESIw) physisorptionexperiments. The multipoint BET surface areas calculated

from nitrogen physisorption measurements at �196 1C are

3310 m2g�1 for 2 and 3770 m2g�1 for 1. The pore volumes are

1.78 cm3 g�1 and 2.03 cm3 g�1, respectively. The hydrogen

adsorption capacities are 1.48 wt% for 1 and 1.21 wt% for 2 at

1 bar and �196 1C.

The Bn-ChirUMCM-1 was tested as the stationary phase

for the HPLC column. Particles with spherical shape of less

than 100 mm and a narrow particle size distribution are

important requirements for a good stationary phase of high

performance liquid chromatography. Since the as-synthesized

particles are much too large and needle-shaped, they were

manually pestled (Fig. S20, ESIw). Fractionation could not be

performed, because of the limited amount of the samples.

Unfortunately, the crushing process gives a broad particle size

and shape distribution (estimated from the SEM image,

Fig. S20, ESIw), which seems not to be easily reproducible.

Nevertheless, to control the packing quality, the pressure drop

of the columns was measured after the packing procedure with

a flow of 0.5 ml min�1 n-heptane at 30 1C. Tests for the

stability of the MOF were made by dispersing the Bn-Chir-

UMCM-1 in isopropanol. From the XRD (Fig. S2, ESIw) itcan be seen that the crystal structure of the material retains. To

guarantee the same packing quality, only Bn-ChirUMCM-1

columns are used which have pressure drops between 25 and

30 bar. All other columns have been rejected. For the comparison

between the UMCM-1 column and the Bn-ChirUMCM-1

column, a more densely packed unmodified UMCM-1 column

with a pressure drop of 70 bar was used.

Thus, shorter retention times on the unmodified UMCM-1

column cannot be caused by an inferior packing quality but

must be caused by the linker modification with the chiral

auxiliary.

Since the chiral auxiliary group of the Bn-ChirUMCM-1 is

a (4S)-benzyl-2-oxazolidinone, oxazolidinones were chosen as

appropriate analytes in the first attempt. Indeed one can

clearly see a selective interaction with the selector, because

on the unmodified UMCM-1 column no retention was observed,

whereas on the chirally modified UMCM-1 a significant

retention occurs. Unfortunately, we could not find an enantio-

selective interaction on the chirally modified UMCM-1

(see Table S2, ESIw). Probably, the difference in the free

adsorption enthalpies of the enantiomers is too small to

observe enantioseparation on that short column. Thus, we

decided to choose analytes expecting a stronger interaction

with the chiral selector by hydrogen bonding. Therefore,

2-butanol, as a representative of a chiral aliphatic alcohol,

Fig. 1 (a) Structure of iPr-ChirUMCM-1 (1). (b) Structure of

Bn-ChirUMCM-1 (2). Left: view along the c axis; Right: micropore

containing the chiral fragment (only one position is shown for

disordered oxazolidinone groups). Hydrogen atoms are omitted for

clarity.

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This journal is c The Royal Society of Chemistry 2011 Chem. Commun., 2011, 47, 12089–12091 12091

and 1-phenylethanol, as a representative of a chiral aromatic

alcohol, were tested. Both showed a significant selective

interaction with the chiral column compared to the non-

modified column (see Table S2, ESIw).With 1-phenylethanol as an analyte a much stronger inter-

action with the chiral selector was observed than with 2-butanol.

Furthermore, with the 1-phenylethanol enantiomers enantio-

selective interactions with the chiral selector can be found

(see Table S2, ESIw). Fig. 2 depicts the chromatograms of the

pure 1-phenylethanol enantiomers measured on the chirally

modified Bn-ChirUMCM-1 column (for results on the unmodified

UMCM-1 see Fig. S21, ESIw). The selectivity a and the

resolution RS for the enantiomer separation can be calculated

as 1.6 and 0.65, respectively. The resolution of less than 1

indicates a significant overlap of the peaks, which is due to

their strong tailing. For further optimization of the separation

efficiency, the length of the column must be adapted and/or a

gradient elution is necessary.

The use of 1-phenylethylamine as a 1-phenylethanol analogue

with an amino-function instead of the hydroxyl-function was

not successful, because the interactions were too strong

already even with the unmodified UMCM-1. The same holds

true for the amino acid D,L-alanine.

After around 200 injections the column material was

characterized by nitrogen adsorption and PXRD. No significant

changes were detected.

In summary, we have prepared and characterized two

porous chiral metal–organic frameworks (iPr-ChirUMCM-1

and Bn-ChirUMCM-1). Bn-ChirUMCM-1 was successfully

used as the stationary phase for HPLC applications. Namely,

1-phenylethanol as analyte showed both selective and enantio-

selective interactions with the MOF. The potential for enantio-

separation can be clearly seen from the selectivity, which is

high enough to reach enantiomer separation. However, the

resolution was too low to reach peak separation under the

chosen conditions. The results presented herein are promising

for the proof of principle and in the future these valuable chiral

materials should be useful for the separation of enantiomers in

the liquid phase.

The authors thank the German Research Foundation with-

in the priority program ‘‘Porous MOFs’’ (SPP 1362) for

financial support. The authors are grateful to the BESSY staff

(Dr U. Mueller, Dr M. S. Weiss) for support during the

measurements and the HZB for financing the travel costs to

BESSY II.

Notes and references

z Crystal data for 1: C50H32NO15Zn4, M = 1148.25, hexagonal, a =41.459(6), c= 17.561(4) A, V= 26140(7) A3, T= 293 K, space groupP63, Z = 6, 80 884 reflections measured, 28 147 unique (Rint =0.0501). The final R1 was 0.0532 and wR2 was 0.1181 (all data). 2:C54H30NO15Zn4, M = 1194.27, hexagonal, a = 41.414(6), c =17.637(3) A, V = 26197(7) A3, T = 293 K, space group P63, Z =6, 83 244 reflections measured, 28 628 unique (Rint = 0.0354). The finalR1 was 0.0533 and wR2 was 0.1115 (all data).

CCDC 831931 and CCDC 831930 contain the supplementarycrystallographic data for 1 and 2, respectively.

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Fig. 2 Chromatogram of 1-phenylethanol enantiomers using Bn-

ChirUMCM-1.

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